Sarah Aitken, MBChB, PhD
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About
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Assistant Professor
Biography
Sarah Aitken, MBChB PhD FRCPath, is an Assistant Professor of Pathology and a member of the Center of Molecular and Cellular Oncology (CMCO) at Yale Cancer Center. She is a Pathologist Clinician Scientist, specializing in gastrointestinal and molecular pathology.
Dr Aitken trained in Medicine (MBChB) at the University of Edinburgh, UK, with an intercalated BMedSci in Experimental Pathology and postgraduate MSc in Translational Medicine. She undertook a mixed experimental-computational PhD at the CRUK Cambridge Institute (University of Cambridge, UK), followed by an EMBO Fellowship in bioinformatics at the IRB Barcelona (Spain). She returned to Cambridge to complete her clinical residency in Histopathology (FRCPath) as an NIHR Academic Clinical Fellow and subsequently NIHR Clinical Lecturer. Prior to joining Yale University, Dr Aitken was an independent Group Leader at the University of Cambridge and Consultant Pathologist (Board Certified Attending) at Cambridge University Hospitals NHS Foundation Trust (UK).
Dr Aitken’s lab uses genomic pathology, which combines molecular biology, genomics, and image analysis, to study mechanisms of mutagenesis, the genetic and epigenetic basis of carcinogenesis, and the consequences of genetic diversity on cancer evolution.
Departments & Organizations
Education & Training
- Clinical Lecturer & Pathology Resident
- University of Cambridge (2021)
- EMBO Visiting Fellow
- IRB Barcelona (2018)
- PhD
- University of Cambridge , Medical Science (2018)
- Academic Clinical Fellow & Pathology Resident
- Cambridge University Hospitals NHS Foundation Trust (2014)
- MSc
- University of Edinburgh, Translational Medicine (2014)
- MBChB
- University of Edinburgh, Medicine and Surgery (2010)
- BMedSci
- University of Edinburgh, Experimental Pathology (2007)
Advanced Training & Certifications
- Fellow of the Royal College of Pathologists (FRCPath)
- Royal College of Pathologists (2021)
- Certificate of Higher Autopsy Training (CHAT)
- Royal College of Pathologists (2019)
Board Certifications
Histopathology
- Certification Organization
- General Medical Council (UK)
- Original Certification Date
- 2021
Research
Overview
Medical Research Interests
ORCID
0000-0002-1897-4140- View Lab Website
Lab Website
Research at a Glance
Publications Timeline
Research Interests
Neoplasms
DNA Damage
DNA Repair
Mutagenesis
Carcinoma
DNA Replication
Publications
Featured Publications
Strand-resolved mutagenicity of DNA damage and repair
Anderson C, Talmane L, Luft J, Connelly J, Nicholson M, Verburg J, Pich O, Campbell S, Giaisi M, Wei P, Sundaram V, Connor F, Ginno P, Sasaki T, Gilbert D, López-Bigas N, Semple C, Odom D, Aitken S, Taylor M. Strand-resolved mutagenicity of DNA damage and repair. Nature 2024, 630: 744-751. PMID: 38867042, PMCID: PMC11186772, DOI: 10.1038/s41586-024-07490-1.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsDNA damageDNA damage-induced mutationsSingle-base resolutionCancer genome evolutionDamage-induced mutationsRepair of DNA damageNucleotide excision repairGenome evolutionMultiple distinct mutationsDNA accessibilityGenomic conditionsReplicative strandProcess genomesDNA base damageTranslesion polymerasesExcision repairDNAMutation patternsMutationsBase damageRepair efficiencyStrandsAlkyl adductsReplicationIdentity fidelityDNA lesion bypass and the stochastic dynamics of transcription-coupled repair
Nicholson M, Anderson C, Odom D, Aitken S, Taylor M. DNA lesion bypass and the stochastic dynamics of transcription-coupled repair. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2403871121. PMID: 38717857, PMCID: PMC11098089, DOI: 10.1073/pnas.2403871121.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsTranscription-coupled repairRNA polymerase IIDistribution of mutationsStalling of RNA polymerase IITranscription-coupled repair (TCRDNA damageGene expressionBarriers to gene expressionSites of DNA damageGenome-wide distributionBarrier to transcriptionDamaged DNA strandMammalian model systemsDNA lesion bypassGene bodiesPolymerase IIRNA polymeraseGenetic integrityGene productsDNA base damageLesion bypassAlkylation damageDNA strandsBypass lesionsMutationsSingle-mitosis dissection of acute and chronic DNA mutagenesis and repair
Ginno P, Borgers H, Ernst C, Schneider A, Behm M, Aitken S, Taylor M, Odom D. Single-mitosis dissection of acute and chronic DNA mutagenesis and repair. Nature Genetics 2024, 56: 913-924. PMID: 38627597, PMCID: PMC11096113, DOI: 10.1038/s41588-024-01712-y.Peer-Reviewed Original ResearchCitationsMeSH Keywords and ConceptsConceptsMutational processesUV damageGenome evolutionGenome-wideTranscribed regionsGenome replicationCancer genomesUV mutationCC dinucleotidesDNA mutagenesisSister cellsDriving evolutionGenomeMutagenesisPunctuated burstsSingle cellsRounds of genome replicationMutationsStrandsCellsMitosisDinucleotideSisterROSReplicationThe artificial intelligence-based model ANORAK improves histopathological grading of lung adenocarcinoma
Pan X, AbdulJabbar K, Coelho-Lima J, Grapa A, Zhang H, Cheung A, Baena J, Karasaki T, Wilson C, Sereno M, Veeriah S, Aitken S, Hackshaw A, Nicholson A, Jamal-Hanjani M, Swanton C, Yuan Y, Le Quesne J, Moore D. The artificial intelligence-based model ANORAK improves histopathological grading of lung adenocarcinoma. Nature Cancer 2024, 5: 347-363. PMID: 38200244, PMCID: PMC10899116, DOI: 10.1038/s43018-023-00694-w.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsTitration of RAS alters senescent state and influences tumour initiation
Chan A, Zhu H, Narita M, Cassidy L, Young A, Bermejo-Rodriguez C, Janowska A, Chen H, Gough S, Oshimori N, Zender L, Aitken S, Hoare M, Narita M. Titration of RAS alters senescent state and influences tumour initiation. Nature 2024, 633: 678-685. PMID: 39112713, PMCID: PMC11410659, DOI: 10.1038/s41586-024-07797-z.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsTumor typesOncogenic RAS-induced senescenceInfluence tumor initiationProgenitor-like featuresTumor-initiating phenotypeSingle-cell RNA sequencing analysisModel in vivoHCC subclassesModel in vitroHepatocellular carcinomaTumor suppressor mechanismEarly tumorigenesisTumor initiationEarly-onsetProgenitor featuresInduce tumorsSuppressor mechanismTumorLate-onsetRNA sequencing analysisOncogenic stressRas-induced senescenceIn vivoMolecular signaturesOncogene dosageConvergent somatic mutations in metabolism genes in chronic liver disease
Ng S, Rouhani F, Brunner S, Brzozowska N, Aitken S, Yang M, Abascal F, Moore L, Nikitopoulou E, Chappell L, Leongamornlert D, Ivovic A, Robinson P, Butler T, Sanders M, Williams N, Coorens T, Teague J, Raine K, Butler A, Hooks Y, Wilson B, Birtchnell N, Naylor H, Davies S, Stratton M, Martincorena I, Rahbari R, Frezza C, Hoare M, Campbell P. Convergent somatic mutations in metabolism genes in chronic liver disease. Nature 2021, 598: 473-478. PMID: 34646017, DOI: 10.1038/s41586-021-03974-6.Peer-Reviewed Original ResearchMeSH Keywords and ConceptsConceptsSomatic mutationsConvergent evolutionNon-alcoholic fatty liver diseaseMetabolic genesAlcohol-related liver diseaseFatty liver diseaseFrequent convergent evolutionRegulation of metabolic pathwaysLiver diseaseExcess of mutationsLipid droplet metabolismHepatocellular carcinomaBurden of somatic mutationsStorage triacylglycerolsAcquisition of somatic mutationsNuclear exportIndependent clonesChronic liver diseases to hepatocellular carcinomaIncreased clone sizePositive selectionMaster regulatorsTranscription factorsInsulin signalingChronic liver diseaseMetabolic pathwaysPervasive lesion segregation shapes cancer genome evolution
Aitken S, Anderson C, Connor F, Pich O, Sundaram V, Feig C, Rayner T, Lukk M, Aitken S, Luft J, Kentepozidou E, Arnedo-Pac C, Beentjes S, Davies S, Drews R, Ewing A, Kaiser V, Khamseh A, López-Arribillaga E, Redmond A, Santoyo-Lopez J, Sentís I, Talmane L, Yates A, Semple C, López-Bigas N, Flicek P, Odom D, Taylor M. Pervasive lesion segregation shapes cancer genome evolution. Nature 2020, 583: 265-270. PMID: 32581361, PMCID: PMC7116693, DOI: 10.1038/s41586-020-2435-1.Peer-Reviewed Original ResearchMeSH Keywords and ConceptsConceptsChromosome-scale phasingDNA lesionsAcquisition of oncogenic mutationsAlternative allelesGenetic diversityMultiple cell generationsCancer genomesLesion segregationDNA replicationMutagenic DNA lesionsDaughter cellsBase pairsCell divisionCell cycleExogenous mutagensHuman cellsOncogenic selectionOncogenic mutationsMouse liver tumorsDNACell generationDNA base pairsMutationsCellsGenomeSomatic mutations and clonal dynamics in healthy and cirrhotic human liver
Brunner S, Roberts N, Wylie L, Moore L, Aitken S, Davies S, Sanders M, Ellis P, Alder C, Hooks Y, Abascal F, Stratton M, Martincorena I, Hoare M, Campbell P. Somatic mutations and clonal dynamics in healthy and cirrhotic human liver. Nature 2019, 574: 538-542. PMID: 31645727, PMCID: PMC6837891, DOI: 10.1038/s41586-019-1670-9.Peer-Reviewed Original ResearchMeSH Keywords and ConceptsConceptsChronic liver diseaseHepatocellular carcinomaLiver diseaseCirrhotic liverMutational burdenSomatic mutationsMutational signaturesProgression to chronic liver diseaseSynchronous hepatocellular carcinomaNon-malignant hepatocytesExcessive alcohol intakeComplexity of hepatocellular carcinomaBands of fibrosisNon-alcoholic fatty liver diseaseStructural variantsFatty liver diseaseGenome of hepatocellular carcinomaClinical spectrumAlcohol intakeLiver failureViral hepatitisClonal expansionMalignant transformationHealth to diseaseRegenerative nodulesMutational landscape of a chemically-induced mouse model of liver cancer
Connor F, Rayner T, Aitken S, Feig C, Lukk M, Santoyo-Lopez J, Odom D. Mutational landscape of a chemically-induced mouse model of liver cancer. Journal Of Hepatology 2018, 69: 840-850. PMID: 29958939, PMCID: PMC6142872, DOI: 10.1016/j.jhep.2018.06.009.Peer-Reviewed Original ResearchMeSH Keywords and ConceptsConceptsSomatic single nucleotide variantsCarcinogen-induced mouse modelsModel of hepatocellular carcinomaMouse model of liver cancerMutational landscape of tumorsModel of liver cancerLandscape of tumorsHepatocellular carcinomaMouse modelMutational landscapeLiver cancerOncogenic drivers of HCCLiver tumorsNon-synonymous point mutationsGenomic alterationsHuman diseasesTruncating mutations of APCMutational signaturesMouse model of hepatocellular carcinomaSingle nucleotide variantsDrivers of hepatocellular carcinomaChemically-induced mouse modelCopy number alterationsCOSMIC mutational signaturesActivating hotspot mutationsCTCF maintains regulatory homeostasis of cancer pathways
Aitken S, Ibarra-Soria X, Kentepozidou E, Flicek P, Feig C, Marioni J, Odom D. CTCF maintains regulatory homeostasis of cancer pathways. Genome Biology 2018, 19: 106. PMID: 30086769, PMCID: PMC6081938, DOI: 10.1186/s13059-018-1484-3.Peer-Reviewed Original ResearchMeSH Keywords and ConceptsMeSH KeywordsAnimalsBreast NeoplasmsCCCTC-Binding FactorCell LineChromatinDNA, NeoplasmEnhancer Elements, GeneticFemaleFibroblastsGene Expression Regulation, NeoplasticGenomeHemizygoteHomeostasisHumansLiver Neoplasms, ExperimentalMiceMice, Inbred C57BLMice, TransgenicProtein BindingSignal TransductionUterine NeoplasmsConceptsTranscriptional regulationIntra-TAD interactionsSteady-state gene expressionCancer-related pathwaysMammalian genomesCTCF occupancyGenome functionChromatin loopsEvolutionary conservationChromatin structureGenomic dysregulationRegulatory domainHemizygous cellsEpigenomic profilingCTCFCTCF expressionMammalian cellsExpressed genesAffinity binding eventsTranscriptional alterationsGene expressionMouse lineagesCancer pathwaysMouse model systemHuman cancers
Academic Achievements & Community Involvement
honor CRUK Clinician Scientist Fellowship
National AwardCancer Research UKDetails09/01/2023United Kingdomhonor Sir Nicholas Wright Lecture and Medal
National AwardPathological Society of Great Britain & IrelandDetails01/27/2021United Kingdomhonor Gold Research Medal
National AwardRoyal College of Pathologists, UKDetails11/21/2019United Kingdomhonor Trainee Research Award
National AwardPathological Society of Great Britain & IrelandDetails12/06/2018United Kingdom